title: Pulmonary toxicity of printer toner following inhalation and intratracheal instillation.
abstract: The pulmonary effects of a finished toner were evaluated in intratracheal instillation and inhalation studies, using toners with external additives (titanium dioxide nanoparticles and amorphous silica nanoparticles). Rats received an intratracheal dose of 1 mg or 2 mg of toner and were sacrificed at 3 days, 1 week, 1 month, 3 months and 6 months. The toner induced pulmonary inflammation, as evidenced by a transient neutrophil response in the low-dose groups and persistent neutrophil infiltration in the high-dose groups. There were increased concentrations of heme oxygenase-1 (HO-1) as a marker of oxidative stress in the bronchoalveolar lavage fluid (BALF) and the lung. In a 90-day inhalation study, rats were exposed to well-dispersed toner (mean of MMAD: 3.76 µm). The three mass concentrations of toner were 1, 4 and 16 mg/m(3) for 13 weeks, and the rats were sacrificed at 6 days and 91 days after the end of the exposure period. The low and medium concentrations did not induce neutrophil infiltration in the lung of statistical significance, but the high concentration did, and, in addition, upon histopathological examination not only showed findings of inflammation but also of fibrosis in the lung. Taken together, the results of our studies suggest that toners with external additives lead to pulmonary inflammation and fibrosis at lung burdens suggest beyond the overload. The changes observed in the pulmonary responses in this inhalation study indicate that the high concentration (16 mg/m(3)) is an LOAEL and that the medium concentration (4 mg/m(3)) is an NOAEL.
authors.affiliation: Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health , Kitakyushu , Japan .
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morimoto
authors.forename: Takako
authors.initials: T
authors.lastname: Oyabu
authors.forename: Masanori
authors.initials: M
authors.lastname: Horie
authors.forename: Tatsunori
authors.initials: T
authors.lastname: Kambara
authors.forename: Hiroto
authors.initials: H
authors.lastname: Izumi
authors.forename: Etsushi
authors.initials: E
authors.lastname: Kuroda
authors.forename: Otto
authors.initials: O
authors.lastname: Creutzenberg
authors.forename: Bernd
authors.initials: B
authors.lastname: Bellmann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Pohlmann
authors.forename: Sven
authors.initials: S
authors.lastname: Schuchardt
authors.forename: Tanja
authors.initials: T
authors.lastname: Hansen
authors.forename: Heinrich
authors.initials: H
authors.lastname: Ernst
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002452:Cell Count; D054360:Chemokine CXCL1 / Q000378:metabolism; D054426:Chemokine CXCL2 / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D003308:Copying Processes; D005260:Female; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D053758:Nanoparticles / Q000633:toxicity; D019055:No-Observed-Adverse-Effect Level; D011327:Printing; D051381:Rats; D017208:Rats, Wistar; D012822:Silicon Dioxide / Q000633:toxicity*; D053260:Soot / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*
chemical_list: D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D019743:Chemokines, CXC; C513297:Cxcl1 protein, rat; C513296:Cxcl2 protein, rat; C513294:Cxcl3 protein, rat; D053260:Soot; C009495:titanium dioxide; D012822:Silicon Dioxide; D014025:Titanium; D051547:Heme Oxygenase-1